Familial Mediterranean fever (FMF) is an autosomal recessive disease frequently seen in non-Ashkenazi Jews, Arabs, Armenians, and Turks. The main clinical features include periodic attacks of fever and serositis, sometimes complicated with amyloidosis. The underlying molecular defect is unknown. After the FMF gene (designated MEF) was mapped to 16p13, an international consortium was formed by the laboratories listed above to facilitate the cloning of the MEF gene. Genetic mapping by the consortium has localized MEF to an 1 cM interval. Our laboratory is mainly involved in the physical mapping effort. We have identified a set of YAC, P1 and PAC clones with STSs developed in the region. These clones contain about 1000 kb of non-overlapping sequences which belong to two contigs of 600 kb and 400 kb in size, on either side of the potential gene location. Additional genomic clones are being isolated which will fill the gap between these two contigs. Moreover, several transcripts have been identified in the region through exon trapping. Full-length cDNAs are being isolated and will be characterized as candidate genes.